A Probabilistic Human Health Risk Assessment for Environmental Exposure to Dibutylphthalate

In the European Union, Directive 92/32/EC and EC Council Regulation (EC) 793/93 require the risk assessment of industrial chemicals. In this framework, it is agreed to characterise the level of “risk” by means of the deterministic quotient of exposure and effects parameters. Decision makers require that the uncertainty in the risk assessment be accounted for as explicitly as possible. Therefore, this paper intends to show the advantages and possibilities of a probabilistic human health risk assessment of an industrial chemical, dibutylphthalate (DBP). The risk assessment is based on non-cancer endpoints assumed to have a threshold for toxicity. This example risk assessment shows that a probabilistic risk assessment in the EU framework covering both the exposure and the effects assessment is feasible with currently available techniques. It shows the possibility of comparing the various uncertainties involved in a typical risk assessment, including the uncertainty in the exposure estimate, the uncertainty in the effect parameter, and the uncertainty in assessment factors used in the extrapolation from experimental animals to sensitive human beings. The analysis done did not confirm the reasonable worst-case character of the deterministic EU-assessment of DBP. Sensitivity analysis revealed the extrapolation procedure in the human effects assessment to be the main source of uncertainty. Since the probabilistic approach allows determination of the range of possible outcomes and their likelihood, it better informs both risk assessors and risk managers.     

NO synthesis in human saliva

Human saliva contains nitrate that is converted into nitrite by the activity of facultative, anaerobic bacteria of the oral cavity. Nitrite can be reduced to NO in the acidic gastric milieu; some NO may also form in the mouth at acidic pH values. In this paper, we show that bacteria ( S. salivarius , S. mitis and S. bovis ) isolated from saliva, may contribute to NO production in human saliva. NO formation by bacteria occurs at neutral pH values and may contribute to the antibacterial activity of saliva.     

Maynard Smith,optimization, and evolution

Maynard Smith’s defenses of adaptationism and of the value of optimization theory in evolutionary biology are both criticized. His defense does not adequately respond to the criticism of adaptationism by Gould and Lewontin. It is also argued here that natural selection cannot be interpreted as an optimization process if the objective function to be optimized is either (i) interpretable as a fitness, or (ii) correlated with the mean population fitness. This result holds even if fitnesses are frequency-independent; the problem is further exacerbated in the frequency-dependent context modeled by evolutionary game theory. However, Eshel and Feldman’s new results on “long-term” evolution may provide some hope for the continuing relevance of the game-theoretic framework. These arguments also demonstrate the irrelevance of attempts by Intelligent Design creationists to use computational limits on optimization algorithms as evidence against evolutionary theory. It is pointed out that adaptation, natural selection, and optimization are not equivalent processes in the context of biological evolution. It is a pleasure to dedicate this paper to the memory of John Maynard Smith. Thanks are due to James Justus and Samir Okasha for comments on an earlier draft.     

A Comparison of Methods for Heat-Mediated Antigen Retrieval for Immunoelectron Microscopy: Demonstration of Cytokeratin No. 18 in Normal and Neoplastic Hepatocytes

Postembedding antigen retrieval is a veil established technique for immnoelectron microscopy; however, many antigens cannot be detected without additional unmasking procedures. This study was undertaken to determine whether microwave oven heating, autoclaving, and pressurized boiling, which are well recognized methods of antigen retrieval for light microscopy, and simple boiling can also be used in electron microscopy. We investigated neoplastic and normal hepatocytes using a commercially available mouse monoclonal antibody against cytokeratin NO. 18 (CK18). The tissue was fixed in paraformaldehyde / gintaraldehyde and embedded in Lowicryl K4M at -40 C. Ultrathin sections in various buffers were exposed to heat using one of four methods or to pronase at 37 C before incubation with the primary antibody. The secondary antibody was gold-labeled goat anti-mouse antibody. Sections that were not heat-treated remained unlabeled, but heat-treated sections showed immu-noreactivity located mainly at the cytoplasmic periphery. Some of the gold particles lay in direct or loose association with intermediate filaments, some were seen in the area of desmosomes, and some did not appear related to any structures. No difference in immunostainlng was found among the four methods of heat treatment. The citrate buffer, pH 6.0, and 10 mM EDTA, pH 8.0, generated the best labeling results.     

小偃6号小麦稳产性和适应性分析

利用１９８０－１９９５年品种比较试验资料和大面积生产中的有关资料对陕西关中地区小麦骨干品种小偃６号进行综合分析。结果表明,小偃６号稳产的原因是：抗病性好、抗逆性强、适应性广、产量构成三要素协调。     

Sterol-phospholipid interactions in model membranes Effect of polar group substitutions in the cholesterol side-chain at C20 and C22

The interactions of phospholipids with four different cholesterol derivatives substituted with one OH or one keto group at position C₂₀ or C₂₂ of the side-chain were studied. The derivatives were the 22,R-hydroxy; 22,S-hydroxy; 22-keto- and 20,S-hydroxycholesterol. Two aspects of the interactions were investigated: (1) the effect of the cholesterol derivatives on the gel → liquid crystalline phase transition of dipalmitoylphosphatidylcholine (DPPC) and of dielaidoylphosphatidylethanolamine (DEPE) monitored by differential scanning calorimetry and (2) The effect on the lamellar → hexagonal H_II phase transition of DEPE monitored by DSC and by ³¹P-NMR to determine structural changes. The gel → liquid crystalline phase transition was affected by the cholesterol derivatives to a much larger extent in the case of DPPC than of DEPE. In both cases, there was a differential effect of the four derivatives, the 22,R-hydroxycholesterol being the less effective. In DPPC-sterol 1:1 systems, 22,R-hydroxycholesterol does not suppress the melting transition, the ΔH values becomes 7.1 kcal · mol^?1 as compared to 8.2 kcal · mol^?1 for the pure lipid. 22,S-OH cholesterol has a much stronger effect (ΔH = 3.1 kcal · mol^?1) and 22-ketocholesterol suppresses the transition completely. In DEPE mixtures of all these compounds, the melting transition of the phospholipid is still observable. The transition temperature was shifted to lower values (?13.5°C in the presence of 20,S-OH cholesterol). The ΔH of the transition was lowered by these compounds except in DEPE-22,R-OH cholesterol mixtures and the cooperativity of the transition (reflected by the width at half peak height) was reduced. The lamellar → hexagonal H_II phase transition was also affected by the presence of these cholesterol derivatives. The transition temperature value was depressed with all these compounds. 20,S-OH cholesterol was the most effective followed by 22,R-OH cholesterol. The ΔH of the transition was not strongly affected. The molecular interfacial properties of these derivatives were studied by the monomolecular film technique. It is most likely that 22,R-OH cholesterol due to the hydroxyl groups at the 3β- and 22,R-positions orients with the sterol nucleus lying flat at the air/water interface, since the compression isotherm of either the pure sterol or the DOPC-sterol mixture (molar ration, 1:1) monomolecular film exhibits a transition at approx. 103 Ų, corresponding to the area of revolution of the sterol nucleus. This remarkable property, due probably to the existence of a kink between the side-chain and the long axis of the steroid nucleus, might explain the smaller effect of this sterol on the melting transition of either PC or PE systems.     

“Menstrual induction” with sulproston

The PGE₂-analogue Sulproton (16-phenoxy·ω-17,18,19,20-tetranor-PGE₂-mythylsulfonylamide) was administered to 200 medically and gynecologically normal women who were 17±0.4 days beyond their expected menstrual period and who had a positive pregnancy test. The intramuscular impact dose (500 μg repeated after 4 hours) caused an immediate tonic uterine contraction which compromised the estradiol 17β, progesterone and chorionic gonadotropin production within the fetoplacental unit, and thereby allowed the evolution of cyclic uterine activity, cervical dilatation and tissue expulsion.Pregnancy termination was complete in 92% of women, 5.5% required surgical curettage and 2.5% were given a second Sulproston treatment 2–3 weeks after the first to remove retained tissue from the uterus. The medical induction of menstruation was preferred by 83% of the women who had previously experienced surgical termination of pregnancy. Normal menstruation resumed in all women after 36±0.9 days. The majority of 42 women questioned found Sulproston a satisfactory, safe, simple and effective drug regimen for “menstrual induction”.     

Phylogenetic analyses of Bradyrhizobium symbionts associated with invasive Crotalaria zanzibarica and its coexisting legumes in Taiwan

In this study, the genetic diversity and identification of Bradyrhizobium symbionts of Crotalaria zanzibarica, the most widely-distributed invasive legume in Taiwan, and other sympatric legume species growing along riverbanks of Taiwan were evaluated for the first time. In total, 59 and 54 Bradyrhizobium isolates were obtained from C. zanzibarica and its coexisting legume species, respectively. Based on the multilocus sequence analysis (MLSA) of concatenated four housekeeping genes (dnaK-glnII-recA-rpoB gene sequences, 1901 bp), the 113 isolates displayed 53 unique haplotypes and grouped into 21 clades. Of these clades, 11 were found to be congruent to already defined Bradyrhizobium species, while the other 10 clades were found to not be congruent to any defined species. In particular, the C. zanzibarica isolates belong to 14 MLSA clades, six of which overlapped with the isolates of coexisting legumes. According to the nodA gene sequences (555 bp) obtained from the 105 isolates, these isolates were classified into three known nodA clades, III.2, III.3 and VII and were further clustered into 10 groups. Furthermore, the C. zanzibarica isolates were clustered into 8 nodA groups, five of which overlapped with the isolates from coexisting legumes. Additionally, the nodA genes of the isolates from native species were dominated by Asian origin, while those from C. zanzibarica were dominated by American origin. In conclusion, C. zanzibarica is a promiscuous host capable of recruiting diverse Bradyrhizobium symbionts, some of which are phylogenetically similar to the symbionts of coexisting legumes in Taiwan.     

US-guided Diffuse Optical Tomography: Clinicopathological Features Affect Total Hemoglobin Concentration in Breast Cancer

PURPOSE: To investigate breast cancers total hemoglobin concentration (THC) characteristics and its association with clinical pathologic findings. MATERIALS AND METHODS: The study was approved by the institutional review board and all patients provided written informed consent. 447 breast cancer patients, totally 455 lesions were included in our study. The size and THC of breast lesions were measured by conventional ultrasound (US) and US-guided Diffuse Optical Tomography (DOT) 1–2?days before surgery. Clinical and pathology information of patients was collected. RESULT: The average THC values of ER- or PR- lesions were significantly higher than the positive ones (P?=?.005 and P?=?.01,respectively); The average THC values of axillar LN+ or LVI+ were higher than the negative ones (P?=?.042 and P?=?.043, respectively). No significant THC difference was found in groups of infiltrating vs. non-infiltrating, HER2+ vs. HER2-, Ki67 high vs. Ki67 low, and different menstrual phases (P?=?.457, P?=?.917, P?=?.417, P?=?.213, respectively).The incidence ages and the lesion-nipple distances of T3 patients were lower than that of T1 and T2 (P?<?.001 and P?<?.001 respectively). The THC values and Ki67 indexes of T2 and T3 lesions were similar, but were higher than that of the T1 group (P?<?=0.001 and P?=?.006, respectively). CONCLUSION: Clinicopathological features of breast cancer, such as ER and PR status, axillary lymph node metastasis, lymphovascular invasion, correlate with THC values. Furthermore, the Ki67 indexes can be predicted using tumor size and THC, useful for pre-surgical evaluation of cancer biology and real-time, non-invasive monitoring of NAC efficacy.